Hydrogenation of ergosterol

We have already reported that the use of cyclohexanol at 140°C in the hydrogenation of ergosterol over Cu/A1203 gives the 5(5 derivative with an 81% selectivity owing to an intramolecular hydrogen transfer reaction, whereas direct H2 addition over the same catalyst gives the 5a isomer with 89% selectivity (10) (Scheme 1). 

Solvent quality controls the hydrogenation of ergosterol (or its acetate) over Raney nickel.116 When pure ethyl acetate is used, for example, reduction proceeds smoothly to 5a -ergost-7-en-3/3-ol, but the presence of a little acetaldehyde, 4-dimethylaminobenzaldehyde, dimethylaniline, or a similar contaminant, stops the reaction at the 7,22-diene stage. 

An isomerization step is also involved in the hydrogen transfer reaction of steroidal homoallylic alcohols which takes place in the presence of Cu/AlaOa 12). This process recently allowed us to obtain 95% 5P Isomer in the hydrogenation of ergosterol under inert atmosphere while 98% 5a isomer was obtained under Ha pressure with the same catalyst [3],... 

The biosynthetic pathway of ergosterol is shown in Figure 15 to explain the steps of inhibition by morpholines the accumulating sterols are framed. Inhibition of the A -reduction by fenpropimorph should lead to an accumulation of 4,4-dimethyl- A8, -ergo-statriene-ol. However, C -demethylation and side chain hydrogenation are obviously able to occur with the accumulating sterol as substrate... 

Imidazoles (ketoconazole, miconazole, fenticonazole, clotrimazole, isoconazole, tioconazole) interfere with fungal oxidative enzymes to cause lethal accumulation of hydrogen peroxide they also reduce the formation of ergosterol, an important constituent of the fungal cell wall which thus becomes permeable to intracellular constituents. Lack of selectivity in these actions results in important adverse effects. 

Bond.— Side chain dehydrogenation is reviewed by Lederer. Unlike the dehydrogenations of the steroid nucleus, introduction of the Irons A -double bond of ergosterol and related steroids does not require the presence of a or A -double bond. However, the suggested formation of ergosta-5,7,22,24(28)-tetraen-3) -ol is supported by incorporation studies. The stereochemistry of this process is species-dependent. In protozoa Ochromonas tetrahymena) the (22R)- and (23S)-hydrogens of cholesterol are lost, i.e. the hydrogens at these positions derived from [2R- H,3R]- and [3R,5R-... 

Ergosteryl acetate hydrogenated 6 hrs. with Raney-Ni in ethyl acetate containing 4-dimethylaminobenzaldehyde -> 5,6-dihydroergosteryl acetate. Y 95%. Also with ergosterol, f. additives, and hydrogenation of the side chain double bond s. W. Tadros and A. L. Boulos, Helv. 58, 668 (1975). 

Additional C-atoms (see the formula of ergosterol, Fig. 120) in the side chains of certain sterols derive from the methyl group of L-methionine. When there are additional ethyl side chains, e.g., in stigmasterol and jff-sitosterol (Fig. 120), two subsequent methylations take place. One hydrogen atom of the methyl group of L-methionine is lost during the methylation (Fig. 123). The mechanism in this respect resembles that of the synthesis of tuberculostearic acid from oleic acid (D 3.2.1). 

A year later, Inhoffen and coworkers made an extensive study of the oxidation products derived from ergosterol, and in 1933, Chuang using the information of both earlier groups noted that after reduction of ergosterol with hydrogen (H2) over... 

The structures of the adducts of ergosterol acetate and maleic anhydride, the first of which were isolated by Windaus and Lutringhaus in 1931, have been revised. 8 Qne is a normal adduct of endo configuration, in which the dienophile addition has occurred from the a-side. The others are produced by an addition at C-7 and concomitant abstraction of either the 9a or the 14a hydrogen to give the 7a-succinic anhydride derivatives of 3p-acetoxy-5,8,22-triene and 3p-acetoxyergosta-5,8 (14), 22-triene. Similar addition to the diene system with acrylonitrile and dimethyl diazodicarboxylate has been observed.85... 

A number of phytosterols contain a two-carbon side chain (ethyl or ethylidene) attached to C-24, the atom which is methylated in the formation of ergosterol. The scheme of Castle et al., reproduced partially in Fig. 2, was originally proposed to account for the formation of such compounds. It was postulated that the 24-methylene compound (structure IV) might be further methylated to yield the 24-ethyl or ethylidene compounds. Evidence in favor of such double methylations has been supplied by the findings that (1) the label from [methyl- C] methionine is incorporated equally into both carbon atoms C-28 and C-29 (Castle et al., 1963 Bader et al., 1964 Villanueva et al., 1964), and (2) 24-ethyli-dene compounds may be converted to the 24-ethyl compounds by whole Pinus pinea seed (van Aller et al., 1969). That the details of the reactions may differ is indicated by deuterium labeling patterns. In some cases, only four hydrogen atoms derived from methionine are incorporated... 

The utility of tricarbonyliron fragments as protecting groups for 1,3-dienes has been demonstrated first by Barton et al. They showed that the diene system in the B ring of ergosterol can be protected by formation of the tricarbonyliron adduct to allow selective catalytic hydrogenation of the side chain A -double bond (Scheme 4-157). ... 

Ergosterol (a triene) rapidly takes up 1 mole of hydrogen selectively to give 5a,6-dihydroergosterol, recrystallized from methanol-chloroform, mp 173-174°. 

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